Mechanical stretch suppresses BMP4 induction of stem cell adipogenesis via upregulating ERK but not through downregulating Smad or p38

Lee, Jeong Soon; Ha, Ligyeom; Park, Jin Hee; Lim, Jung Yul

doi:10.1016/j.bbrc.2012.01.010

Cited by 28 publications

(17 citation statements)

References 31 publications

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“…Aside from the activation of canonical Smad signaling, increasing evidence indicates that the MAPKs, mainly ERK1/2 and p38 MAPK, were also activated by BMP4 in various cell types, including human PASMCs (12,14,(33)(34)(35). The functional outcomes of MAPK activation by BMP4 have been linked mostly to proliferative responses, and to the regulation of various gene expressions related to cell growth and differentiation (12,14,(36)(37)(38). Similarly, we found that BMP4 caused the activation of p38 and ERK1/2 in rat distal PASMCs, although the time-course activation patterns of p38 and ERK1/2 were different from each other, and were also somewhat different from what was documented for human peripheral PASMCs (14,39).…”

Section: Discussionmentioning

confidence: 99%

BMP4 Increases Canonical Transient Receptor Potential Protein Expression by Activating p38 MAPK and ERK1/2 Signaling Pathways in Pulmonary Arterial Smooth Muscle Cells

et al. 2013

Am J Respir Cell Mol Biol

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Abnormal bone morphogenetic protein (BMP) signaling has been implicated in the pathogenesis of pulmonary hypertension. We previously found that BMP4 elevated basal intracellular Ca 21 ([Ca 21 ] i ) concentrations in distal pulmonary arterial smooth muscle cells (PASMCs), attributable in large part to enhanced store-operated Ca 21 entry through store-operated Ca 21 channels (SOCCs). Moreover, BMP4 up-regulated the expression of canonical transient receptor potential (TRPC) proteins thought to compose SOCCs. The present study investigated the signaling pathways through which BMP4 regulates TRPC expression and basal [Ca 21 ] i in distal PASMCs. Real-time quantitative PCR was used for the measurement of mRNA, Western blotting was used for the measurement of protein, and fluorescent microscopic for [Ca 21 ] i was used to determine the involvement of p38 and extracellular regulated kinase (ERK)-1/2 mitogen-activated protein kinase (MAPK) signaling in BMP4-induced TRPC expression and the elevation of [Ca 21 ] i in PASMCs. We found that the treatment of BMP4 led to the activation of both p38 MAPK and ERK1/2 in rat distal PASMCs. The induction of TRPC1, TRPC4, and TRPC6 expression, and the increases of [Ca 21 ] i caused by BMP4 in distal PASMCs, were inhibited by treatment with either SB203580 (10 mM), the selective inhibitor for p38 activation, or the specific p38 small interfering RNA (siRNA). Similarly, those responses induced by BMP4 were also abolished by treatment with PD98059 (5 mM), the selective inhibitor of ERK1/2, or by the knockdown of ERK1/2 using its specific siRNA. These results indicate that BMP4 participates in the regulation of Ca 21 signaling in PASMCs by modulating TRPC channel expression via activating p38 and ERK1/2 MAPK pathways. [Ca 21 ] i in PASMCs during chronic hypoxia, and relaxed arteries in chronically hypoxic rats (5). Store-operated calcium channels (SOCCs) are believed to be composed of members of transient receptor potential canonical (TRPC) family, which assemble as either homotetramer or heterotetramer channels and mediate store-operated calcium entry (SOCE) (6). We recently demonstrated the predominant expression of TRPC1, TRPC4, and TRPC6, and the presence of SOCE in PASMCs (7). Exposure to chronic hypoxia enhanced the expressions of TRPC1, TRPC6, and SOCE in rat distal PASMCs (1, 2). Using a specific small interfering (si)RNA individually targeted to TRPC1 and TRPC6, we found they both contributed to the hypoxic enhancement of SOCE and the maintenance of elevated basal [Ca 21 ] i in PASMCs (8). These studies provided fundamental information indicating that the elevation of basal [Ca 21 ] i in PASMCs during chronic hypoxia are in large part caused by enhanced SOCE via the up-regulation of TRPC proteins.Bone morphogenetic protein (BMP) family members comprise multifunctional cytokines that play crucial roles during embryonic development, organogenesis, and adult tissue remodeling by regulating cell proliferation, growth, differentiation, and apoptosis (9). BMP4,...

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Section: Discussionmentioning

confidence: 99%

BMP4 Increases Canonical Transient Receptor Potential Protein Expression by Activating p38 MAPK and ERK1/2 Signaling Pathways in Pulmonary Arterial Smooth Muscle Cells

et al. 2013

Am J Respir Cell Mol Biol

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“…In our own study, it was shown for the first time that cyclic stretch (10% strain, 0.25 Hz) applied during the MSC commitment stage (before the adipogenic induction period) could suppress MSC adipogenic differentiation [9]. If C3H10T1/2 MSCs were stretched during the BMP4 pre-treatment period (commitment period), the subsequent response of the cells to adipogenic hormonal inducers was suppressed.…”

Section: Mechanical Stimulation; Mechanotransductionmentioning

confidence: 98%

“…This study on cell compression, though it is not for MSCs, suggests a similarity with the cyclic stretch inhibition of adipogenesis described above. Also, the blockage of SGBS adipogenesis by the compression applied before the adipocytic induction period may be analogous with the cyclic stretch suppression of MSC adipogenesis when applied during the commitment period [9]. Since most of the cell compression studies have had a goal to improve the chondrogenesis of MSCs, more studies on the adipogenic lineage at varying compression regimens and for different types of adipose precursor cells are needed to provide a complete comparison.…”

Section: Mechanical Stimulation; Mechanotransductionmentioning

confidence: 98%

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Mechanical Control of Mesenchymal Stem Cell Adipogenesis

Stoll¹,

Hamel²,

Lee³

et al. 2015

Endocrinol Metab Syndr

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Increased Mesenchymal Stem Cell (MSC) commitment and differentiation into adipocytes contributes to obesity. Other than dietary and biochemical factors, recent studies have begun to explore the role of mechanical signals in controlling MSC adipocytic commitment and differentiation. Several reported data suggest that by subjecting MSCs to certain mechanical stimuli, such as stretching, compression, and fluid shear, their adipogenesis could be inhibited or decreased. However, it is still very early to draw conclusions on the detailed mechanical regimens to optimally inhibit MSC adipogenesis and on the molecular pathways governing such adipogenesis-inhibitory mechanosensitive signaling. In this commentary, key data on the mechanical control of MSC adipogenesis and proposed molecular mechanisms will be highlighted and a future perspective in this new topic area will be provided.

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“…Here, it was found that the cellular stretch did not affect BMP4-inducted activation in Smad or p38, as which this pathway would normally signal through Smad 1/5/8 and p38MAPK, but instead the tensile stretch caused significant ERK1/2 phosphorylation. When ERK signalling is blocked, the stretch suppression of BMP4-induced MSC adipogenesis was significantly deteriorated, suggesting that stretch suppresses BMP4-induced adipogenesis via upregulating ERK [41]. …”

Section: The Effect Of Tensile Strain On Progenitor Cell Proliferatiomentioning

confidence: 99%

Mechanical stretch and chronotherapeutic techniques for progenitor cell transplantation and biomaterials

Rogers¹,

Pekovic-Vaughan²,

Hunt³

2018

BioMedicine

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In the body, mesenchymal progenitor cells are subjected to a substantial amount external force from different mechanical stresses, each potentially influences their behaviour and maintenance differentially. Tensile stress, or compression loading are just two of these forces, and here we examine the role of cyclical or dynamic mechanical loading on progenitor cell proliferation and differentiation, as well as on other cellular processes including cell morphology, apoptosis and matrix mineralisation. Moreover, we also examine how mechanical stretch can be used to optimise and ready biomaterials before their implantation, and examine the role of the circadian rhythm, the body’s innate time keeping system, on biomaterial delivery and acceptance. Finally, we also investigate the effect of mechanical stretch on the circadian rhythm of progenitor cells, as research suggests that mechanical stimulation may be sufficient in itself to synchronise the circadian rhythm of human adult progenitor cells alone, and has also been linked to progenitor cell function. If proven correct, this could offer a novel, non-intrusive method by which human adult progenitor cells may be activated or preconditioned, being readied for differentiation, so that they may be more successfully integrated within a host body, thereby improving tissue engineering techniques and the efficacy of cellular therapies.

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Mechanical stretch suppresses BMP4 induction of stem cell adipogenesis via upregulating ERK but not through downregulating Smad or p38

Cited by 28 publications

References 31 publications

BMP4 Increases Canonical Transient Receptor Potential Protein Expression by Activating p38 MAPK and ERK1/2 Signaling Pathways in Pulmonary Arterial Smooth Muscle Cells

BMP4 Increases Canonical Transient Receptor Potential Protein Expression by Activating p38 MAPK and ERK1/2 Signaling Pathways in Pulmonary Arterial Smooth Muscle Cells

Mechanical Control of Mesenchymal Stem Cell Adipogenesis

Mechanical stretch and chronotherapeutic techniques for progenitor cell transplantation and biomaterials

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